Reversing DNA damage caused by the sun before it becomes skin cancer may be possible

SAN DIEGO, April 5 -Scientists have synthesized an artificial enzyme they believe can repair sun-damaged DNA, the cause of many skin cancers. Although promising, they emphasize that much more research needs to be done before it's known if the enzyme can be used to protect people. Each year, more than a million new cases of skin cancer are reported in the United States, many from overexposure to the sun.

The research was reported here today at the 221st national meeting of the American Chemical Society, the world's largest scientific society, by Marco Jonas, Ph.D. One of a team of University of Notre Dame researchers investigating the enzyme's cancer prevention potential, Jonas is hopeful that it may someday lead to a protective after-the-fact sunscreen or other product.

The artificial enzyme the researchers created is patterned after an enzyme produced by the E. coli bacterium discovered more than 50 years ago by other researchers. The Notre Dame group is one of several doing research in this area of DNA repair.

Particular molecules, known as thymine dimers, are formed in DNA as a result of ultraviolet radiation. These dimers are a "major cause of skin cancer," according to Jonas. Simply put, the enzyme works by attaching itself to the dimers and breaking them down, thus reversing the damage caused by UV light before cancer develops.

It usually takes many years for skin cancer to occur, if ever, after overexposure to the sun, Jonas said. Because of this, he thinks it should be possible to repair the DNA damage years after the exposure, provided it's done before the cancer has a chance to gain a foothold.

The research team has specifically shown that their artificial enzyme does recognize and break up the thymine dimers outside of DNA.

"The question is, can we do it in a real piece of DNA," said Olaf Wiest, Ph.D., team leader of the Notre Dame research group. "We have high hopes that it will do the same thing when the dimer is part of a piece of DNA."

The researchers estimate it will be about four months before they are ready to test the enzyme in DNA.

For every drug that makes it to market, "you make about 10,000 compounds," Wiest pointed out. Despite these formidable odds, he is optimistic.

"I'm pretty excited about it. This lays the foundation for a [potential] drug. I think it's promising."

If the artificial enzyme is successful in the upcoming DNA tests, it will likely go through many modifications as it proceeds through further laboratory testing. Then, it would have to be turned over to other researchers for laboratory and clinical studies.

Even if it passes all testing, Jonas estimates that it would be at least ten years or more before a product might come to market that could repair DNA damage caused by the sun.

The paper on this research, ORGN 663, will be presented at 8:20 a.m., Thursday, April 5, at the San Diego Convention Center, Room 7B.

Marco Jonas, Ph.D., is a postdoctoral researcher in the department of chemistry and biochemistry at the University of Notre Dame in Notre Dame, Ind.

Olaf Wiest, Ph.D., is an assistant professor in the department of chemistry and biochemistry at the University of Notre Dame in Notre Dame, Ind.

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